Leptin Receptor Gene Polymorphisms Research Articles

Association of insulin resistance and leptin receptor gene polymorphism in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes. In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3. Hardy-Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively). Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.

The Role of Leptin Receptor Gene Polymorphism in the Formation of Insulin Resistance in Children

The Role of Leptin Receptor Gene Polymorphism in the Formation of Insulin Resistance in Children

Association of Leptin Receptor Gene Polymorphisms with Keloids in the Chinese Han Population.

BackgroundThe association between leptin receptor (LEPR) polymorphisms and keloids is still unclear. Our study aimed to explore the association between LEPR gene polymorphisms and keloids in the Chinese Han population.Material/MethodsWe implemented a case-control study in a cohort of 352 keloid patients and 299 healthy controls to analyze the correlation between 4 SNPs (rs1137101, rs1938496, rs6588147, and rs7555955) and keloids. Genomic DNA was extracted from peripheral blood by using TGuide M16 (Tiangen). Genotyping of LEPR SNPs was performed using an improved multiple ligase detection reaction (iMLDR) by Shanghai Genesky Bio-Tech Co., Ltd.ResultsWe found that patients caring the AA genotype of rs1137101 and the CC genotype rs1938496 tend to have the increased risk of keloids (P=0.026, P=0.047). Carrying the GA, AA gene type, and G allele frequencies of rs7555955, patients were more likely to have to keloids (P=0.030, P=0.016, P=0.018, respectively). There were no significant differences in genotype distribution and allele frequencies of rs6588147 between cases and controls. The association of rs1137101 and rs7555955 under dominant, recessive, and allele models exhibited significant differences among family-history keloid patients, no-family-history keloid groups, and normal controls (χ2=6.471, P=0.039; χ2=6.477, P=0.039; χ2=6.197, P=0.045, respectively). Similarly, the OR of rs1137101 in the recessive model was significantly higher in patients with a family history of keloids than those in controls. Nonetheless, there are significant ORs of rs1938496 and rs6588147 among the mild-moderate keloid, severe keloid, and control groups.ConclusionsThe LEPR gene polymorphisms are associated with keloid formation and severity, especially in patients with a positive family history.

Obesity in Children with Leptin Receptor Gene Polymorphisms.

The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald's sequential analysis, Spearman's correlation analysis, analysis of nominal data and multiple discriminant analysis. 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald's analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

The Effect of Leptin Receptor Gene Polymorphisms (R223Q and P1019P) in Susceptibility to Polycystic Ovarian Syndrome in Kurdish Women.

BackgroundPolycystic ovary syndrome (PCOS) is the known endocrinopathy disorder in the reproductive phase of women’s life. More than half of the women with PCOS suffer from obesity which impacts the ovarian functions by leptin levels. Here the R223Q and P1019P polymorphisms of leptin receptor (LEPR) gene were examined in PCOS patients of Kurdish women from west of Iran.Materials and MethodsIn this case-control study, one hundred women with PCOS and 100 healthy women bearing similar age range were selected based on Rotterdam diagnostic criteria. Polymerase chain reaction-restriction frag- ment length polymorphism (PCR-RFLP) method was used to genotype polymorphisms LEPR (R223Q and P1019P), by respectively the BsaWI and NcoI restriction enzymes. Pearson’s chi-square (χ2) test was used to analyze the vari- ation in genetic distributions and unconditional logistic regression model was used to calculate the odds ratio (OR; 95% CI).ResultsGenotype frequencies of the R223Q and P1019P polymorphisms showed significant difference between the patients with PCOS compared to the controls. G allele (R223Q) reduced the risk of PCOS about 0.49-fold (P<0.001). While, T allele (P1019P) increased the risk of PCOS 2.69-fold (P<0.001).ConclusionIt can be concluded that the R223Q and P1019P polymorphisms showed a significant association with PCOS susceptibility risk. It seems that G allele (R223Q) with reducing OR had a protective effect on this syndrome, while T allele (P1019P) with increasing OR was a risk factor for PCOS.

The Inter-Relation between Leptin Receptor (Q223R) Gene Polymorphism and the Risk of Egyptian Patients with HCC.

Background:The relationship of leptin (LEP) and polymorphism of leptin receptor (LEPR) were studied in patients with hepatocellular carcinoma (HCC) and compared with those with liver cirrhosis to find out the extent of the risk of LEPR on patients with HCC. Methods:Serum LEP level and LEPR Q223R gene polymorphism were determined in 300 patients with liver disease categorized equally into five groups’ healthy volunteers, patients with hepatitis C (HCV), patients with non-alcoholic steatohepatitis (NASH), liver cirrhosis and HCC. LEPR gene was amplified by polymerase chain reaction (PCR) then digested by the MSP1 restriction enzyme. Results:The isolated 212 bp of LEPR was sequenced. The serum LEP level was reduced in patients with cirrhotic and HCC. Serum LEP level had negatively correlated with both tumor grade and size in HCC patients. The data obtained from restriction fragment length polymorphismPCR and sequencing revealed the existence of a novel synonymous Q223R single nucleotide polymorphism (SNP) in exon 223 of LEPR gene (1137101). LEPR Gln223Arg, GG and GA genotypes were found in all studied groups. LEPR Gln223Arg, AA genotype was found in NASH, HCC, and control. LEPR Gln223Arg GA genotype is associated with some patients with HCC. Conclusion:GA genotype of LEPR Gln223Arg may be regarded as a probable genetic risk factor for Egyptian patients with HCC.

Leptin G-2548A and Leptin Receptor Q223R Gene Polymorphisms are Differently Associated with Oxidative Process in Mexican Mestizo and Indigenous with Obesity.

The aim of this study was to examine whether plasma lipid peroxidation, antioxidant capability, leptin levels are associate selected LEP -2548 A/G and LEPR Q223R polymorphisms in mestizo and indigenous obesity Mexican population. We identified and characterized 50 overweight or obese subjects and 50 healthy, normal- weight volunteers with indigenous Tepehuana or Mexican mestizo ethnicity from Durango, Mexico. LEP -2548 A/G and LEPR Q223R polymorphisms were determined by genotyping. Concentrations of leptin, antioxidant capacity (CA) and lipoperoxidation (LIPX) were determined in fast conditions on plasma with Enzyme-Linked ImmunoSorbent Assay (ELISA) in all participants. The highest genotype frequency was the heterozygous LEPR, which was associated with lipid peroxidation levels in normal-weight Tepehuan populations. A positive correlation was observed (r = 0.5; p <0.01) between LEP polymorphism and lipoperoxidation in normal weight Tepehuan subjects. On the other hand, the LEPR polymorphism was associated with the level of lipoperoxidation (r = 0.13; P <0.05) in mestizo populations of normal weight. It is probable that there is a synergistic effect for obesity, where the presence of oxidative stress and single nucleotide polymorphisms (SNP) of leptin and its receptor contributes to the generation of pathological subcutaneous fat of obesity, together with the environmental conditions of the populations.

Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation

BackgroundWe aimed to examine whether combined donor/recipient variants in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes may affect outcomes in renal transplantation. MethodsA total of 233 donors and their corresponding 307 recipients were genotyped for LEPR rs1805094, rs1137100 and rs1137101, and ADIPOQ rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF), graft loss and estimated glomerular filtration rate (eGFR). ResultsRecipients whose donors carried variant alleles of LEPR rs1137100 and rs1137101 had lower risk of DGF [OR = 0.48 (0.24–0.97), p = 0.040] and [OR = 0.47 (0.23–0.95), p = 0.035], respectively. In addition, rs1137101 also showed an inverse association with lower incidence of graft loss [OR = 0.44 (0.31–0.97), p = 0.040]. The analysis of genetic scores of donor/recipients showed that again rs1137101 was inversely associated with both outcomes: OR = 0.46 (0.23–0.92), p = 0.029 and OR = 0.45 (0.11–0.81), p = 0.009, respectively. With regard to graft function, the T-allele of ADIPOQ rs1501299 in the donor was related to higher eGFR values (75.26 ± 29.01 vs. 67.34 ± 25.39 ml/min for wild-type grafts, p = 0.012). Higher combined genetic scores in this same polymorphism were also associated with better function (78.33 ± 31.87 vs. 68.25 ± 24.32 ml/min, p = 0.018). Finally, eGFR values were similar between paired kidneys but they were different when comparing grafts with or without the rs1501299 T-variant (77.87 ± 26.50 vs. 69.27 ± 26.73 ml/min, p = 0.016). ConclusionsOur study has shown for the first time to our knowledge that variants in LEPR and ADIPOQ genes of the donors and/or their combination with those in the recipients may affect the outcome of renal transplantation.

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

BackgroundLeptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia.MethodsA matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted.ResultsGenotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy–Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98–10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15–10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77–113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09–0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16–11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D′ = 1, r2 = 0.012).ConclusionsOur data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.

Detection of polymorphisms in the bovine leptin receptor gene affects fat deposition in two Chinese beef cattle breeds.

Leptin receptor (LEPR) gene play a pivotal role in the regulation of fat deposition and energy homeostasis. This study investigated the presence and frequency of polymorphisms of bovine LEPR gene and determine whether the polymorphisms are associated with the fat deposition in two Chinese beef cattle breeds. Quantitative real-time polymerase chain reactions identified that the expression of LEPR gene was highest in the liver and subcutaneous fat. Four single nucleotide polymorphisms (SNPs) were identified including g.24169C>T, g.24256T>A, g.24267 G>C and g.24413T>A. A greater backfat thickness was associated with the AA genotype of g.24256T>A compared to the TT genotype. A greater intramuscular fat content was associated with the GG genotype of g.24267 G>C compared to the CC genotype. Both g.24169C>T and g.24413T>A were not correlated with fat deposition. These results indicated that the SNP g.24256T>A and g.24267 G>C of LEPR gene may be useful markers for genetic improvement of fat deposition in Chinese beef cattle breeds.

Association of LEPR gene polymorphisms with the risk of hepatitis B virus-related liver disease in Guangxi Chinese: A case-control study

Background and objective: Leptin receptor (LEPR) signaling inhibits apoptosis, promotes angiogenesis and proliferation, and plays a critical role in carcinogenesis. Variants of the LEPR gene may be key factors in the growth of human malignant tumors. However, the relationship between LEPR polymorphisms and hepatocellular carcinoma (HCC) has not been thoroughly investigated. Therefore, we further investigated the association between LEPR polymorphisms and the risk of chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis (LC), and HCC in a southern Guangxi Chinese population.Method: Two LEPR polymorphisms (rs1137100 and rs1137101) were genotyped in 138 CHB patients, 136 patients with LC, 149 HCC patients, and 146 healthy controls using the SNaPshot method.Results: We did not observe any significant difference in the LEPR rs1137100 and rs1137101 polymorphisms between the groups of healthy controls and patients (all p > 0.05), regardless of genotypes, alleles, or haplotypes.Conclusions: Our data suggest that the genetic variants of the LEPR gene are not associated with the risk of HBV-related liver diseases (CHB, LC, and HCC) in the Guangxi population. Further studies are necessary to validate these results.

Role of serum leptin levels and leptin receptor gene polymorphisms in systemic lupus erythematosus.

Serum leptin and leptin receptor gene polymorphisms may play a role in the etiopathogenesis of SLE. This study was undertaken to explore the relationship between serum leptin levels and leptin receptor (LEPR) gene polymorphisms with susceptibility to SLE in Egyptian population and to study their relationships with clinical, laboratory, radiographic findings, and disease activity of SLE (SLEDAI). A total of 50 unrelated female patients, who met the SLICC classification criteria for SLE and fifty healthy blood donors, matched for age, sex, and BMI with SLE patients, serving as a control group, were included in this study. All participants had completed preliminary questionnaires and clinical, laboratory, and radiographic examinations. Serum leptin levels were measured by ELISA assays. LEPR genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We compared serum leptin levels and LEPR gene polymorphisms in SLE patients and controls, and we tested their relationships with clinical, laboratory, and radiographic findings and SLEDAI in SLE patients. The present study showed significant differences of serum leptin levels between SLE patients and controls (p < 0.001). Moreover, higher frequencies of variant genotype (AA) and (A) allele were found in SLE patients compared to controls (p = 0.008 and 0.001, respectively). No associations were observed between the serum leptin, various LEPR genotypes, and gene alleles and the development of clinical, laboratory, and radiological manifestations. Furthermore, no associations were observed between the various LEPR genotypes or gene alleles and leptin levels (p = 0.633 and 0.337 respectively) in SLE patients. Additionally, no correlations were observed between leptin levels, various genotypes, and alleles with SLEDAI (p = 0.244, 0.741, and 0.838 respectively) in SLE patients. Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian population; however, they are not associated with the development of clinical, lab, and radiological findings. Disease activity is neither correlated with serum leptin level nor associated with LEPR gene polymorphism. Serum levels of leptin are not associated with LEPR gene polymorphism. Key Points • Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian patients. • Serum leptin is not associated with SLE disease activity.

Impact of obesity on leptin, leptin receptor gene polymorphism, and some adipokines in egyptian patients with knee osteoarthritis

Aim: The aim of this study was to investigate the role of leptin receptor (LEPR) gene polymorphism and adipokines in the pathogenesis of knee osteoarthritis (OA) in Egyptian female patients. Materials and Methods: Ninety-five Egyptian females were classified into three groups: group I (control): 32 healthy females, Group II: included 30 non obese knee osteoarthritic patients and Group III: included 33 obese knee osteoarthritic patients. Genotyping of rs1137101 at LEPR gene was analyzed using allelic discrimination assay by real-time polymerase chain reaction technique, and then, adipokines and nitric oxide (NO) levels were measured. Results: The frequency of GG genotype was found to be significantly higher in Group III when compared to Group II and controls (26% to 4%, 1%) (P Conclusion: Our findings suggested that the genetic variation in rs1137101 is involved in the pathogenesis of both obesity and knee OA in Egyptian female patients. In addition, it seems that adipokines and oxidative stress are important factors linking obesity, adiposity, and inflammation in OA.

Single Nucleotide Polymorphism of Leptin Receptor Gene in Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic disease associated with abnormal glucose metabolism due to insulin resistance. Leptin has been shown to be involved in pathways influencing the risk of cardiovascular disease and diabetes. The aim of the study was to evaluate pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to find its association with serum levels of leptin and also to compare leptin levels in diabetics and non-diabetics. Methodology: The cross-sectional study was conducted in Molecular Genetics division of KS Hegde Medical Academy, Mangalore. Genotyping of leptin receptor was done for Gln223Arg alleles by PCR-RFLP in 39 type 2 diabetics. Serum leptin was assayed using ELISA in 39 cases and 45 non-diabetic controls. Statistical analysis was carried out with Graph pad Instat version 3. Results: Hardy-Weinberg Equilibrium (HWE) for the LEPR gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in diabetics compared to controls. Women in control groups showed significantly higher leptin levels (p<0.05) compared to men. There was no significant association between leptin levels among different genotypic variants. Conclusion: We could conclude that type 2 diabetes mellitus is not associated with LepR gene polymorphism as well as there is independent relationship between LepR gene polymorphism and leptin levels

Leptin Receptor Gene Polymorphisms in Some Turkish Donkey Populations

Leptin receptor is a fundamental regulator in physiological functions of the regulation of food intake, energy homeostasis, immune function, and reproduction as well as on ovarian follicular cells on the placenta and lactating mammary glands. The aim of this study was to investigate the LEPR gene polymorphism in 60 donkeys reared in Thrace region of Turkey. A 585 bp long partial intron 6, exon 7, intron 7, and exon 8 regions of LEPR gene were amplified, and polymerase chain reaction products analyzed via DNA sequencing. A novel single-nucleotide polymorphism (SNP) was identified as g.713668A>G in the seventh exon region of LEPR gene. This novel SNP was first identified, and the partial DNA sequence of LEPR gene in donkeys was reported for the first time in this study, and these sequences were deposited to NCBI Genbank database with the accession number: MK807114-MK807115. The A>G transition revealed a silent mutation (CAA-CAG) in glutamine amino acid. This nucleotide mutation could cause the changes of secondary structure of protein and expression level of LEPR hormone. For this reason, additional studies are needed to reveal new SNPs and in the LEPR gene that may affect economic traits and structure of protein in donkey breeds.

49P - Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer

BackgroundLeptin is produced by adipose tissue of breast and is overexpressed in Breast cancer. Association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with Breast cancer are inconsistent. Only a very few studies have examined this biochemical and genetic variables so we planned to investigate this association and its impact on leptin level and disease characteristics. MethodsStudy included 70 females (40 women with pathological prove of invasive Breast cancer patients and 30 controls). Staging was done according to the American Joint Committee on Cancer 8th edition. LEP and LEPR polymorphisms were estimated by real time PCR. Serum leptin was measured by ELISA. ResultsBoth LEPR rs 1137101 and LEP rs 7799039 increase risk of breast cancer where GG genotype and G allele frequencies of LEPR rs 1137101 were significantly higher in patients than control [52.5% vs 16.7% and 68.8% vs 36.7%] (p = 0.002) and (p < 0.001) respectively. GG genotype increase risk of BC with [OR 9.1: 95% CI 2.30-35.94] while G allele predispose to disease with [OR 3.8: 95% CI 1.87 – 7.70]. Furthermore, LEP rs 7799039 A allele was markedly elevated in patients (61.2%) than healthy ones (43.3%) (p = 0.037) with [OR 2.06: 95% CI 1.05 – 4.08]. Leptin levels were markedly elevated than healthy ones (p < 0.001). ConclusionsResults clarified interesting relation of circulating leptin level and LEP and LEPR polymorphisms with predicting Breast cancer that may be implicated in pathogenesis of disease. Legal entity responsible for the studyMenoufia University. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Association of leptin receptor genetic variants (LEPR) with obesity and leptin level in unexplained infertility in northern Indian population

BackgroundThe leptin receptor (LEPR) gene, is a member of the class I cytokine receptor superfamily, with six known isoforms. Animal as well as human modal both studies indicate that LEPR have important and powerful roles in the mechanism of obesity. This study aims to determine the correlation of the LEPR genetic variant with obesity and leptin level in the obese and control groups in the northern Indian population. Methods109 fertile controls and 120 unexplained infertile cases were recruited. Serum leptin level was measured by active human ELISA kit using an ELISA reader. Leptin receptor gene polymorphism A668G, A326G and G1968C were analyzed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). ResultsThe anthropometric parameters are slightly higher in obese cases as compared to control group (p > 0.005), whereas waist circumference and hip circumference shows a significant p- value (p < 0.005) between obese cases and controls. The leptin level is found increased in obese cases than controls and this difference is significant with p < 0.05. The higher frequency of GG genotype of (Gln223Arg) variant in obese cases with significant difference found in between obese cases and control groups p < 0.001. Similarly GG and CC genotype of (Lys109Arg) and (Lys656Asn) respectively found higher frequency with significantly different p < 0.001 in obese group as compared to control group. ConclusionGenetic variants (Gln223Arg), (Lys109Arg) and (Lys656Asn) in LEPR gene are significantly associated with anthropometric parameter obesity and leptin level in northern Indian population.

Targeted Sequencing Analysis of the Leptin Receptor Gene Identifies Variants Associated with Obstructive Sleep Apnoea in Chinese Han Population

PurposeObstructive sleep apnea (OSA) is a common sleep disorder that is influenced by various environmental and genetic factors. The potential associations of leptin and leptin receptor (LEPR) polymorphisms with OSA have been studied in different populations; however, the results remain inconclusive. The aim of this study was to examine the association between LEPR gene polymorphisms and OSA risk.MethodsA total of 322 samples were used, including 226 OSA subjects and 96 controls. Targeted sequencing of the entire LEPR gene was performed in all subjects. Polysomnography was used to diagnose obstructive sleep apnea. The associations between variants and OSA were determined by multivariate regression analyses.ResultsFour single-nucleotide polymorphisms of LEPR were identified in all subjects. The genotype frequency of locus rs3790435 was significantly different between the OSA and control groups. Specifically, the variant genotype rs3790435 CC in LEPR was associated with a lower risk of OSA (OR 0.462, 95% CI 0.250–0.854, p = 0.014) in a recessive model after controlling for potential confounders. After BMI stratification, obese patients with this variant genotype were found to have a lower risk of developing OSA. Moreover, subjects with the rs3790435 CC genotype were found to have a statistically lower apnea–hypopnea index (AHI) and higher nadir oxygen saturation than the TT/CC genotypes without differences in plasma leptin levels.ConclusionsOur study identified a novel variant of LEPR in patients with OSA, and specifically found an association between rs3790435 polymorphisms and OSA risk in Chinese Han subjects.

Полимофизм гена рецептора лептина и лептинорезистентность при неалкогольной жировой болезни печени, ассоциированной с ожирением

Полимофизм гена рецептора лептина и лептинорезистентность при неалкогольной жировой болезни печени, ассоциированной с ожирением

Is leptin receptor gene (Gln223Arg) polymorphism associated with disease susceptibility and severity in patients of primary knee osteoarthritis?

Aim of the workA significant role of Leptin receptor (LEPR) is documented in inflammation, body weight homeostasis and maintenance of cartilage. This study was conducted to detect the existence of genetic association between Knee osteoarthritis (KOA) susceptibility and severity; and LEPR (Gln223Arg) single nucleotide polymorphism (SNP). Patients and methods73 primary KOA patients and 73 matched healthy controls were studied. Kellgren Laurence (K/L) radiographic grading system, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and Visual Analogue Scale (VAS) were used to assess the severity of KOA. LEPR Gln223Arg SNP (rs1137101) was genotyped in KOA patients and controls using polymerase chain reaction-restriction fragment length polymorphism (PCR –RFLP) technique and verified by direct DNA sequencing. ResultsIn the current study, a significant genetic association was found between KOA patients carrying the AA genotype of LEPR and the extent of radiological severity (p < 0.044). In addition, a significant difference was detected within the patients between Body Mass Index (BMI) and the SNP. Patients carrying the wild type (GG) genotype showed lower body mass index (BMI) in comparison to patients carrying the heterozygous (AG) genotype and the mutant (AA) genotype (p < 0.032). However, no direct genetic association was detected between the SNP and KOA. ConclusionLeptin receptor gene (Gln223Arg) SNP might be associated with severity of KOA. There is a significant genetic association between the SNP and BMI hence, LEPR SNP might be indirectly associated with the incidence of KOA. Furthermore, the SNP is not directly associated with KOA susceptibility in the Egyptian population.